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GEN Updates in Biotechnology - Next-Generation Sequencing
Journal of Computational Biology
Robust Sparse Hyperplane Classifiers: Application to Uncertain Molecular Profiling Data

To cite this paper:
C. Bhattacharyya, L.R. Grate, M.I. Jordan, L. El Ghaoui, I.S. Mian. Journal of Computational Biology. December 1, 2004, 11(6): 1073-1089. doi:10.1089/cmb.2004.11.1073.

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C. Bhattacharyya
Department of EECS, University of California Berkeley, Berkeley, CA 94720.
Current address: Department of CSA, Indian Institute of Science, Bangalore 560012, Karnataka, India.
L.R. Grate
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
M.I. Jordan
Department of EECS, University of California Berkeley, Berkeley, CA 94720.
Department of Statistics, University of California Berkeley, Berkeley, CA 94720.
L. El Ghaoui
Department of EECS, University of California Berkeley, Berkeley, CA 94720.
I.S. Mian
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.

Molecular profiling studies can generate abundance measurements for thousands of transcripts, proteins, metabolites, or other species in, for example, normal and tumor tissue samples. Treating such measurements as features and the samples as labeled data points, sparse hyperplanes provide a statistical methodology for classifying data points into one of two categories (classification and prediction) and defining a small subset of discriminatory features (relevant feature identification). However, this and other extant classification methods address only implicitly the issue of observed data being a combination of underlying signals and noise. Recently, robust optimization has emerged as a powerful framework for handling uncertain data explicitly. Here, ideas from this field are exploited to develop robust sparse hyperplanes, i.e., classification and relevant feature identification algorithms that are resilient to variation in the data. Specifically, each data point is associated with an explicit data uncertainty model in the form of an ellipsoid parameterized by a center and covariance matrix. The task of learning a robust sparse hyperplane from such data is formulated as a second order cone program (SOCP). Gaussian and distribution-free data uncertainty models are shown to yield SOCPs that are equivalent to the SCOP based on ellipsoidal uncertainty. The real-world utility of robust sparse hyperplanes is demonstrated via retrospective analysis of breast cancer related transcript profiles. Data-dependent heuristics are used to compute the parameters of each ellipsoidal data uncertainty model. The generalization performance of a specific implementation, designated "robust LIKNON," is better than its nominal counterpart. Finally, the strengths and limitations of robust sparse hyperplanes are discussed.

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